Beta-elemene, method to prepare the same and uses thereof

ABSTRACT

This invention provides an anti-cancer composition of high purity beta-elemene extracted from plant sources. This invention also provides for the use of the composition as well as a low cost method to prepare it by multiple passes through the precision distillation tower.

[0001] Throughout this application, various publications are referencedand full citations for these publications may be found in the text wherethey are referenced. The disclosures of these publications are herebyincorporated by reference into this application in order to more fullydescribe the state of the art as known to the skilled therein as of thedate of the invention described and claimed herein.

BACKGROUND OF THE INVENTION

[0002] Beta-elemene is a chemical compound that can be extracted fromnumerous plants. Curcuma Wenyujin Chen et C. Ling, Curcuma aromatia, andCurcuma longa linn (all belonging to Ziniberaceae) are resources forelemene extraction in China. They grow in tropical areas around theworld. In China they are found primarily in Guangdong, Sichuan Fujian,Guangxi and Zhejiang provinces. More than 50 different plants have beenfound to contain beta-elemene, such as Radix Inulae, Radix Ginseng, E.Wenyujin chen et C. Ling and others.

[0003] Beta-elemene can be extracted from the essential oil contained inplants. In China, about 40 different essences were found to contain morethan 1% beta-elemene. Higher concentrations are found in the essentialoil produced from Magnolia sieboldii, Citrus junos leaves and Aglaiaodorata flower and particularly, G. Cymbopogon winterianus Jowitt.

[0004] G. Cymbopogon winterianus Jowitt is one of the major plantresources for essential oil production in China. The essential oilcontains 1.63-5.21% of beta-elemene and the byproduct of essenceextraction i.e. crude product, contains as much as 80% beta-elemene.

[0005] Currently China produces more than 2000 tons of oil extractedfrom the G. Cymbopogon winterianus Jowitt annually. This production isover 50% of the world total, and it is one of the major essential oilexports for China. G. Cymbopogon winterianus Jowitt provides a richresource from which large quantities of beta-elemene can be extractedeconomically.

[0006] Beta-elemene has the chemical name:

[0007] 1-methyl-1-vinyl-2,4-diisoprotenyl-cyclohexane.

[0008] Beta-elemene is found in elemene in the various extracts, alongwith gamma and delta elemene, which are chemical isomers of thebeta-elemene. The extracts contain other compounds as well and it isvery difficult to isolate beta-elemene from these other compounds usingroutine isolation techniques.

[0009] Preparations made from Curcuma Aromatica Salisb (which containselemene) have been a part of Chinese herbal remedies for centuries. Ithas been used internally and topically for a wide variety of ailments.

[0010] Elemene at various concentrations with other ingredients appearsin applications as diverse as a mosquito repellent(see U.S. Pat. No.5,66,781), burn treatment (see U.S. Pat. Nos. 5,558,914 and 5,384,125)and treatment for Herpes Simplex (see U.S. Pat. No. 5,385,733).

[0011] Of particular interest is the anti-tumor characteristicsexhibited by elemene.

[0012] Yang H, Wang X and Yu L

[0013] Journal article—NIH database ID# 98048492—“THE ANTITUMOR ACTIVITYOF ELEMENE IS ASSOCIATED WITH APOPTOSIS” Chung Hua Chung Liu Tsa Chih;18(3):169-72 1996, Cancer Institute, Zhejiang Medical university,Hangzhou, China

[0014] determined that the anti-tumor activity of elemene is associatedwith cell cycle arrest from S to G2M phase transition and with theinduction of apoptosis. They further demonstrated this effect in vitroand in vivo to human and murine tumor cells.

[0015] All purity and concentration values in this application arereported by volume. The concentration % in a sample is the volume ofbeta-elemene divided by the total volume of the sample, multiplied by100.

[0016] Guo YT

[0017] Journal article—NIH data base ID# 83285582—“ISOLATION ANDIDENTIFICATION OF ELEMENE FROM THE ESSENTIAL OIL OF CURCUMA WENYUJIN”,Chung Yao Tung Pao; 8(3):31 1983) (the present inventors were co-authorsof this paper)

[0018] described the isolation of elemene from Curcuma Wenyujin anddescribed elemene's anti-neoplastic activities. Beta-elemene in aconcentration of 92% was used. The beta-elemene was extracted usingchromatography.

[0019] Wang J, Zhang H, and Sun Y

[0020] Clinical trial-Journal article—NIH data base ID#98048551—PHASEIII CLINICAL TRIAL OF ELEMENUM EMULSION IN THE MANAGEMENT OF MALIGNANTPLEURAL AND PERITONEAL EFFUSIONS” reported the use of elemene emulsionin the management of malignant effusions.

[0021] Shi J

[0022] Journal article—NIH data base ID # 82631581—“Experimentalpharmacological studies on the volatile oil of Wen-E-Zhu (CurcumaAromatica Salisb): Study on the anti-tumor activity ofbeta-elemene”—Zhongyao Tongbao, Luda Inst. Medical and PharmaceuticalSciences, Luda, P.R. China

[0023] demonstrated that the beta-elemene component of elemene exhibitedmarked anti-tumor activity against murine Ehrlich ascites carcinoma andrat ascitic reticulum cell sarcoma. Diarrhea and weight loss werereported as side effects during treatment. The material used containedbeta-elemene 65%, gamma and delta-elemene 20%, and impurities 15%. Thebeta-elemene was extracted by chromatography.

[0024] Fu NW

[0025] Journal article—NIH data base ID #84282970—“ANTITUMOR EFFECT ANDPHARMACOLOGICAL ACTIONS OF BETA-ELEMENE ISOLATED FROM THE RHIZOME OFCURCUMA AROMATICA”, Chung Yao Pao; 9(2):35-9 1984

[0026] reported on the anti-tumor effect of beta-elemene, one of themonomers comprising the elemene isomer. As in Shi. J article above, thematerial used contained beta-elemene 65%, gamma and delta-elemene 20%,and impurities 15%.

[0027] In December 1993 elemene was designated as a Chinese nationalClass II new drug. In February 1994 the anti-cancer effect of elemenewas confirmed by the health authority of the P.R. of China.

[0028] During the 2 year trial of the drug in China, it was determinedthat elemene has not only the ability to manage malignant chest andabdominal ascites, but also had beneficial effects on brain tumors(neuroglioma), liver and esophageal cancer.

[0029] The elemene has apparent anti-cancer activity on mouse EhrlichAscites Carcinoma (EAC) and mouse leukemia P388, L₁₂₁₀, ARS and rat YASetc. From the Chinese phase I, II and III clinical trials, it was provedthat the elemene exhibits some control over cancerous chest andabdominal ascites and surface tumors. The total effect rate was about69%. It should be noted that 27% of the cerebral carcinoma patientsreached CR level with a combination of the elemene and localchemotherapy in the expanded clinical trials.

SUMMARY OF THE INVENTION

[0030] The research conducted demonstrated that the beta-elemenecomponent of elemene had significant anti-tumor characteristics and thatthe primary mechanism was the induction of apoptosis in the tumor cells.

[0031] Previous researchers produced beta-elemene by chromatography,which produced only small quantities of beta-elemene at high cost. Themaximum purity attained had been 92%.

[0032] In addition, work performed in the Department of Embryology ofthe Dalian Medical University revealed that beta-elemene is able to passthrough the brain-blood barrier (BBB) and thus reach tumors within thebrain.

[0033] It is an object of the present invention to provide for ananti-cancer drug wherein the active ingredient is beta-elemene.

[0034] This invention relates generally to compositions of beta-elemeneand method of producing higher concentration than previously possible,produced at reasonable cost using abundant plant sources;pharmaceuticals containing beta-elemene and application of thepharmaceuticals to treat various malignant diseases.

[0035] Since indications for the pharmaceutical composition ofbeta-elemene at the present time are mainly for malignant disorders itis an object of the invention to provide a method for applying thepharmaceutical to treat various malignancies, especially neuroglioma andsolid tumors.

[0036] Having identified the beta-elemene monomer as a component ofelemene with a strong anti-tumor activity, it is a purpose of thepresent invention to provide for a method to produce it in quantity andwith sufficient purity to reduce the side effects from any impurities,and provide a standard dosage. As a result, the governmentalrequirements for pharmaceuticals with respect to analytical definitionand reproducible composition, independent from the variable compositionof the starting material from any of several plants can be fulfilled.

[0037] A further object of the invention is to provide a beta-elemenecomposition of high concentration (96.4-97.2%). A composition withhighly concentrated effective content and minimum impurities is requiredin many countries with high pharmaceutical standards which are notusually met by simple extracts since the norms apply to pure substances.Until now it has not been possible to prepare such high concentrationsof beta-elemene from the plant sources.

[0038] Another advantage of the highly concentrated bete-elemene is thereduced amount that must be dosed to be effective.

[0039] An additional advantage of highly concentrated beta-elemene isthe further removal of inactive substances. The extensive removal ofinactive accompanying substances enhances the safety of thepharmaceutical, since the simpler composition of the active componentconcentrate facilitates a more precise analytical determination of themain components and detection of potential impurities.

[0040] It is a further object of the invention to provide a deliverymeans for effective levels of the beta-elemene to reach surface andinternal tumors.

[0041] It is a further object of the invention to provide a low-costhigh-volume means of production of beta-elemene.

[0042] The present invention is the use and preparation of beta-elemenethat is characterized by a purity of more than 96%. The inventioninvolves the preparation methods and the composition of an anti-cancerdrug, especially with the preparation methods and the composition of ananti-cancer drug in which the beta-elemene is the effective ingredient.

DETAILED DESCRIPTION OF THE INVENTION

[0043] China produces 2000 tons of oil extracted from G. Cymbopogonwinterianus Jowitt. The oil contains 1.63-5.21% beta-elemene. In theprocess of extracting the oil for its essence a by-product, called“crude product”, is produced. This crude product has a higherconcentration of beta-elemene than the original plant material, as highas about 80%. This crude product provides an inexpensive, abundantsource of feed material for this new process.

[0044] This invention provides a composition of 96.4-97.2% beta-elemene.

[0045] The other ingredients are gamma-elemene 0.5% elemenol 0.8-1.2%Copane 1.3-1.7% Isofuranogermacrene approx. 0.2%

[0046] This invention provides a composition of at least 96.4%beta-elemene.

[0047] This invention provides the above compositions having componentsextracted from a group of over 40 plants known to have useful levels ofbeta-elemene.

[0048] This invention provides an injectable formulation containing theabove compositions. The injectable formulation may then be administeredto the subject via different routes, such as intravenous injection,intramuscular injection, intradermal injection, peritoneal injection andinjection into solid tumor.

[0049] This invention provides the above compositions that can be addedinto cream, ointments or presence in raw materials to prepare the same.

[0050] This invention provides a method for obtaining a beta-elemenecomposition using a distillation tower to separate the crude materialinto fractions, the tower being specifically constructed (the precisiondistillation tower) to produce beta-elemene at a concentration of96.4-97.2% and at very low cost.

[0051] This is the first time that the precision distillation tower isused to produce beta-elemene. It is achieved through themulti-fractionation of the crude material in the precision distillationtower.

[0052] The precision distillation tower to be used is designed andmanufactured specifically for this purpose. A tower has a height of 1.4meters, a tower diameter of 6 cm and the tower interior is fitted withas many 3×3 mm hollow 120 mesh stainless steel cylinders as can be fitwithin it. The number of plates within the tower is 40.

[0053] This invention utilizes at least one of the following as thesource of the plant material:

[0054] G. Cymbopogon winterianus Jowitt, Zhangzhou Aglaia odorataflower, Fuzhou Aglaia odorata flower, Chunging Aglaia odorata flower,Chunging Aglaia odorata leaves, Zhangzhou Aglaia odorata leaves, Yibingeranium leaves, Kunmin geranium leaves, Litchi chenensiscinnamomifolium, dry Lauris nobilis, Citrus limona leaves, Vitisvinifera grape leaves, Clausena lansium leaves, Fortunella margaritaleaves, Fortunella oborata, C. Wenyujin Chen, and Magnolia sieboldi.

[0055] This invention provides for a method comprising the followingsteps:

[0056] (A) obtaining as a plant source at least one of the followingplants: G. Cymbopogon winterianus Jowitt, Zhangzhou Aglaia odorataflower, Fuzhou Aglaia odorata flower, Chunging Aglaia odorata flower,Chunging Aglaia odorata leaves, Zhangzhou Aglaia odorata leaves, Yibingeranium leaves, Kunmin geranium leaves, Litchi chenensiscinnamomifolium, dry Lauris nobilis, Citrus limona leaves, Vitisvinifera grape leaves, Clausena lansium leaves, Fortunella margaritaleaves, Fortunella oborata, C. Wenyujin Chen, and Magnolia sieboldi.

[0057] (B) extracting oil from said plant source to produce crudeproduct;

[0058] (C) loading said crude product into the distillation tower toseparate said crude product into fractions; and

[0059] (D) collecting the fraction with the highest concentration ofbeta-elemene, thereby producing a composition with a concentration ofabout 95% beta elemene. The harvest rate for this fraction is about 63%of the input.

[0060] The beta-elemene composition produced in step (D) is furtherconcentrated by a second fractionation comprising the followingadditional step:

[0061] (E) loading the composition comprising about 95% beta-elemeneinto the tower to separate into fractions; and

[0062] collecting the fraction with the highest concentration ofbeta-elemene, thereby producing a composition of beta-elemene with aconcentration of 96.4-97.2%. The harvest rate is about 60%.

[0063] In the preferred embodiment, this invention provides for themethod of obtaining beta-elemene from its plant sources comprising thesteps of:

[0064] (The First Fractionation)

[0065] (a) Obtaining the crude product that is produced as a by-productof elemene essence extraction (such as by the Essence ChemicalFactory-China);

[0066] (b) Loading 2000 g of crude product containing more than 80%beta-elemene into the precision distillation tower.

[0067] The precision distillation tower has a height of 1.4 meters and adiameter of 6 cm. The tower cavity is fitted with as many hollow 3 mm×3mm 120 mesh stainless steel cylinders as can be fit inside. The numberof plates within the tower is 40;

[0068] (c) Establishing a vacuum of not less than 2 mmHG, usuallybetween 2-5 mmHg with a temperature range from 86 to 93 degrees C. and areaction time of about 10 hours. There are 3 different temperatureranges for fractionation; 86-88 degrees C., 89-90 degrees C. and 91-93degrees C. The fraction of 89-90 degree C has the highest concentrationof beta-elemene and is collected. The harvest rate for the fraction of89-90 degrees C. is about 63% of the input. The purity at this point isabout 95%;

[0069] For the Second Fractionation:

[0070] (d) Take 2000 g of the fractionation previously collected fromthe first fractionation with a purity of 95% and repeat the processusing the same parameters as the first fractionation. During thefractionation use 3 temperature ranges: 86-88 degrees C., 89-90 degreesC. and 91-93 degrees C. The fraction from the 89-90 degree C range hasthe highest concentration of beta-elemene and is retained. The harvestrate for the second fractionation is 60% and the purity of thebeta-elemene is 96.4-97.2%;

[0071] (e) The residue remaining in the tower and the fractions at 86-88and 91-93 degrees C. can be further refined or recycled. Recycle theunused fractions from the first pass together with the remaining oilextract in the tower which went through two fractionations by loadingthe tower with these materials. Steps (a) through (d) are repeated andthe fraction at 89-90 degrees C. is collected. The harvest rate is 20%.

[0072] If desired the fractionation can be repeated further, using thesesame steps.

[0073] The final product from the precision distillation contains:beta-elemene 96.4-97.2% copane 1.3-1.7% Elemenol 0.8-1.2% gamma-elemene0.5% Isofuranogermacrene 0.2%

[0074] Beta- and gamma elemene have similar structure and anti-canceractivities.

[0075] Since the fractionation is conducted in a sealed container thereis no environmental pollution.

[0076] The beta-elemene can be used in any pharmaceutically suitablecarrier.

[0077] In the preferred embodiment, prepare the pharmacologicalpreparation from the beta-elemene composition by the following steps:

[0078] (1)Mix the beta-elemene as obtained above with phosphatide andcholesterol, heat to 80 degrees C. until the mix melts down and becomesclear.

[0079] (2)Dissolve NaH2PO4 and Na2HPO4 in water and heat to 80 degreesC.

[0080] (3)Place the mixtures from above steps (1) and (2) into a highspeed emulsifier until the mixtures become emulsive injection.

[0081] (4)Filtrate the emulsive injection through a G4 sintered glassfunnel, and check the particle size.

[0082] (5)Fill the checked emulsive injection into ampules and sealthem. Sterilize at 100 degrees C. for 40 minutes to yield the finalproduct.

[0083] For the purposes of this invention “pharmaceutically suitablecarriers” means any of the standard pharmaceutical carriers. Examples ofsuitable carriers are well known in the art and may include, but notlimited to, any of the standard pharmaceutical carriers such as aphosphate buffered saline solutions, phosphate buffered salinecontaining Polysorb 80, water, emulsions such as oil/water emulsion, andvarious type of wetting agents. Other carriers may also include sterilesolutions, tablets, coated tablets, and capsules.

[0084] Typically such carriers contain excipients such as starch, milk,sugar, certain types of clay, gelatin, stearic acid or salts thereof,magnesium or calcium stearate, talc, vegetable fats or oils, gums,glycols, or other known excipients. Such carriers may also includeflavor and color additives or other ingredients. Compositions comprisingsuch carriers are formulated by well known conventional methods.

[0085] Research Results:

[0086] Using the described procedure to prepare the beta-elemeneanti-cancer drug, the following results were obtained from animalpharmacodynamic studies:

[0087] (A) Ascites carcinoma: intra-peritoneal injection of thebeta-elemene has a stable therapeutic effect on EAC and S₁₈₀ ascitescancer. The life prolongation rates are 85-310% and 90-321%respectively. The life prolongation rate for hepatic ascites carcinomais 103-224%.

[0088] (B) Solid tumor: The beta-elemene injection has some inhibitioneffect on S₁₈₀ solid tumor. The inhibition rate is 33-59%. Theinhibition rate for hepatic solid tumor is 10-30%.

[0089] (C) Murine leukemia L₁₂₁₀: The beta-elemene injection has obvioustherapeutic effect on L₁₂₁₀ leukemia. The life prolongation rate was47-286%.

[0090] (D) Neuroglioma: It was indicated in the pharmacodynamic study ofcerebral neuroglioma using murine sub-renal capsule model that theinhibition rate was 50-70%.

[0091] (E) There was no measurable bone marrow inhibition or reductionof white blood cell count, etc which are common side effects ofconventional anti-cancer drugs.

[0092] Based on the findings of these experiments, the inventors suggestthat beta-elemene has beneficial effects on the treatment of ascitescarcinoma, solid tumor, neuroglioma, murine leukemia etc. with noobvious side effects observed. They further conclude that beta-elemenewas suitable for development as a national (China) class I new drug forhuman cancerous ascites, neuroglioma and solid tumor, and for researchin its use to be continued.

[0093] Human Data:

[0094] In two instances, patients at the Second Affiliated Hospital ofthe Dalian Medical University were treated with the beta-elemenecomposition as an emulsive injection. The medical records were kept atthat hospital.

[0095] Patient I: (Hospitalization #3106) A 25 year old female Patienthad headache, right side arm and leg weakness and hemiplegia. She wasdiagnosed by CT scan as having a thalamic glioblastoma. The tumor sizewas 3.8×5.3×4 cm. The patient was hospitalized for surgery in July 1995.80% of the tumor was excised, but it grew back to the full size withintwo weeks after the operation. A beta-elemene emulsive injection wasemployed through 600 ml cervical artery intubation and 400 mlintravenous drip alternately once per day. The growth of the tumor wasquickly controlled, but on CT scan there was no apparent reduction intumor size. The patients symptoms improved and she survived for 11months with the tumor.

[0096] Patient II: (Hospitalization Number 3679) A 65 year-old female

[0097] The patient had headache, vomiting and gait problems due to lungcancer. A CT scan indicated that the lung cancer had resulted inmultiple metastasis to the brain. The tumor in the right cerebellum was2.8×4.0×3.1 cm. The size of a tumor in the left ganglion basal zone was0.5×1.5×1.6 cm. Due to the lung metastasis and the age of the patient,surgery was difficult to perform. The patient was hospitalized in midNovember 1996.

[0098] It was estimated that she would not survive longer than a month.The patient was treated with beta-elemene as prepared herein. Thepatient received the same regimen as patient I. Her condition improved,the headache was reduced. The vomiting stopped. In the middle ofDecember 1996 the patient had another CT scan. The size of the tumor wasreduced. In March 1997 the patient requested to leave the hospital asthe lung cancer spread to the rib and lymph nodes, along with thepathological left forearm fracture. The prolongation of the life of thepatient was more than 4 months, based upon previous experience withpatients at that stage of illness.

We claim:
 1. A method for producing a composition containingbeta-elemene from a plant source using a distillation tower comprisingthe following steps: (a) obtaining said plant source; (b) extracting oilfrom said plant source to produce crude product; (c) loading said crudeproduct into said distillation tower to separate said crude product intofractions; and (d) collecting the fraction with the highestconcentration of beta-elemene, thereby producing a composition ofbeta-elemene.
 2. A method for producing a composition of beta-elemene asin claim 1 further comprising the following steps: (a) loading saidtower with said fraction collected in said step 1(d); (b) drawingmultiple fractions; and (c) collecting the fraction with the highestconcentration of beta-elemene, thereby producing a composition ofbeta-elemene.
 3. A method as in claim 2 wherein said plant sourcecontains at least one of the following: G. Cymbopogon winterianusJowitt, Zhangzhou Aglaia odorata flower, Fuzhou Aglaia odorata flower,Chunging Aglaia odorata flower, Chunging Aglaia odorata leaves,Zhangzhou Aglaia odorata leaves, Yibin geranium leaves, Kunmin geraniumleaves, Litchi chenensis cinnamomifolium, dry Lauris nobilis, Citruslimona leaves, Vitis vinifera grape leaves, Clausena lansium leaves,Fortunella margarita leaves, Fortunella oborata, C. Wenyujin Chen, andMagnolia sieboldi;
 4. A method for producing a composition ofbeta-elemene as in claim 3 further comprising the following steps: (a)using a precision distillation tower as said distillation tower; (b)establishing a vacuum in said precision distillation tower of 2-5 mmHg;(c) heating said tower to a temperature range of 86-93 degrees C.; (d)using a fraction ratio of between 4:1 and 5:1; and (e) using a reactiontime of about 10 hours.
 5. A method for producing a composition ofbeta-elemene as in claim 4 wherein said vacuum is 2 mmHg and saidfraction ratio is 4:1.
 6. A method for producing a composition ofbeta-elemene as in claim 5 further comprising: (a) a first fractionationcomprising the steps of: producing a fraction at a temperature range of86-88 degrees C.; producing a fraction at a temperature range of 89-90degrees C.; producing a fraction at a temperature range of 91-93 degreesC.; collecting said fraction produced at said temperature range of 89-90degrees C.; removing any residual material remaining in the tower; and(b) a second fractionation comprising the steps of: loading saidcomposition produced at said temperature range of 89-90 degrees C. intosaid precision distillation tower; producing a fraction at a temperaturerange of 86-88 degrees C.; producing a fraction at a temperature rangeof 89-90 degrees C.; producing a fraction at a temperature range of91-93 degrees C.; and collecting said fraction produced at saidtemperature of 89-90 degrees C., thereby producing a composition ofbeta-elemene.
 7. A method as in claim 6 for producing a composition ofbeta-elemene wherein said precision distillation tower furthercomprises: said tower having a height and diameter, wherein said heightis 1.4 meters and said diameter is 6 cm; said tower having an inside andoutside surface wherein said inside surface defines a cavity; 3 mm×3 mmempty 120 mesh stainless steel cylinders, wherein said cavity is fittedwith as many of said stainless steel cylinders as will fit therein.
 8. Amethod for producing a composition of beta-elemene as in claim 7 whereinsaid plant source is G. Cymbopogon winterianus Jowitt.
 9. A method forproducing a composition of beta-elemene as in claim 8 wherein saidcomposition of beta-elemene comprises at least 96% beta-elemene.
 10. Amethod of producing a composition of beta-elemene as in claim 8 whereinsaid composition of beta-elemene comprises between 96.4 and 97.2%beta-elemene.
 11. A method of producing a composition of beta-elemene asin claim 8 wherein said composition comprises: about 96.4-97.2%beta-elemene; about 0.8-1.2% elemenol; about 1.3-17% copane; about 0.5%gamma-elemene; and about 0.2% isofuranogermacrene.
 12. A method forproducing a composition of beta-elemene as in claim 6 further comprisingrecycling the byproducts of said fractionation.
 13. A method as in claim6 further comprising: combining said fractions produced at saidtemperature ranges of 86-88 and 91-93 degrees C. with the residueremaining after fractionation; and loading said tower with saidcombination.
 14. The composition produced by the method of claim1,2,3,4,5,6,7,8,9,10,11,12 or
 13. 15. A composition for treating cancercomprising at least 96% beta elemene.
 16. A composition for treatingcancer as in claim 15 further comprising elemenol, copane andisofuranogermacrene.
 17. A composition for treating cancer comprising96.4-97.2% beta-elemene.
 18. A composition for treating cancercomprising: about 96.4-97.2% beta-elemene; about 0.5% gamma-elemene;about 0.8-1.2% elemenol; about 1.3-1.7% copane; and about 0.2%isofuranogermacrene.
 19. A composition to treat glioma comprising aneffective amount of beta-elemene and a pharmaceutically suitablecarrier.
 20. A composition to treat neuroglioma comprising an effectiveamount of beta-elemene and a pharmaceutically suitable carrier.
 21. Amethod for treating cancer in a subject comprising: administering tosaid subject an effective amount of beta-elemene and a pharmaceuticallysuitable carrier.
 22. A method as in claim 21 wherein said compositionis administered orally, intravenously, topically or by injection intosolid tumor.
 23. A method of inducing cellular apoptosis comprisingcontacting the cell with an effective level of beta-elemene.
 24. Amethod of inducing cellular apoptosis comprising contacting a cell withthe beta-elemene composition as produced in claim1,2,3,4,5,6,7,8,9,10,11,12 or
 13. 25. A method of inducing cellularapoptosis in tumor cells in a subject comprising administering to saidsubject an effective level of beta-elemene and a pharmaceuticallysuitable carrier.
 26. A precision distillation tower device forproducing a composition of beta elemene comprising: said tower having aheight and diameter, wherein said height is 1.4 meters and said diameteris 6 cm; said tower having an inside and outside surface wherein saidinside surface defines a cavity; 3 mm×3 mm hollow 120 mesh stainlesssteel cylinders, wherein said cavity is fitted with as many of saidstainless steel cylinders as will fit therein.